Chronic Sepsis Research Articles

A descriptive study of the etiology and outcome of peripheral vascular injuries at the Aminu Kano Teaching Hospital

Background: Peripheral vascular injuries (PVIs) are infrequent but their management could be hampered by delayed presentation and fraught with untoward morbidity or death. Herein, we describe the factors contributing to the morbidity and mortality of PVIs in this environment. Materials and Methods: Data relating to patients with PVIs between March, 2012 and March, 2018 were retrospectively collected from case folders and analyzed. Results: The records of 16 patients were analyzed. There were 13 (76.9%) males and 3 (23.1%) females. The male/female ratio was 4.3:1. The median age was 30 years (range, 10–52). The median duration between injury and presentation was 2.5 days. Nine (56.3%) PVIs were secondary to stab wounds; two (12.5%) occurred in intravenous drug abusers while the others were each of different etiologies. The superficial femoral artery was the most frequently injured vessel (six cases; 37.6%). Fourteen (87.5%) patients required surgery ranging from patch arterioplasty to reversed saphenous vein interposition graft. Two (12.5%) patients were managed conservatively. The mean length of stay for the overall patient population was 11.7 days. Ten patients (62.5%) had surgical site infections (SSIs) causing prolonged hospital admission. There were three deaths (18.8%), all occurring in patients with co-morbidities like chronic kidney disease (CKD) and sepsis. Conclusion: PVIs were infrequent in this environment and presentation is delayed. Reasonable limb salvage rates are possible depending on the severity of ischemia. SSIs may suggest prolonged hospital stay. Mortality appears to be heightened if there are underlying co-morbidities. More patients would however be required to statistically correlate these findings.

Role of high-sensitivity troponin T as a sensitive biomarker for postoperative myocardial infarction and outcome after isolated coronary artery bypass grafting surgery

Background Uncertainty exists about the diagnosis of post-coronary artery bypass grafting (CABG) Perioperative myocardial infarction (PMI) owing to nonconsensus for elevated biomarkers diagnostic levels and associated criteria. Post-CABG studies concerning high-sensitivity troponin (hs-TnT) and its role in the diagnosis of postoperative MI are few. Aim We are aiming to figure out the diagnostic and prognostic role of hs-TnT in individuals undergoing isolated coronary artery bypass graft surgery and whether it has relations to other diagnostic criteria. Patients and methods A total of 50 patients with multivessel coronary artery disease who elected for isolated CABG were enrolled in the study. Our exclusion criteria included individuals with chronic renal impairment, sepsis, and pre-existing high level of hs-TnT (unless >50% increment significantly raises its postoperative difference). Moreover, patients who experienced marked intraoperative hypotension (mean arterial blood pressure 5 min) were excluded. Levels of 140 ng/l (10 times 99th percentile upper reference limit) and 500 ng/l (10 times coefficient of variation of 10% for fourth-generation troponin T applied to hs-TnT) were predetermined. Results We enrolled 50 patients who underwent elective CABG. Their mean age was 59.8 ± 6.5 years, and there were 30 (60%) males. hs-TnT level was significantly associated with a higher incidence of off-pump CABG, higher cardiopulmonary bypass time, and higher aortic cross-clamp time. The composite morbidity was significantly higher in patients with hs-TnT level more than 500 (P Conclusion The occurrence of post-CABG MI is associated with a higher level of hs-TnT as well as a higher incidence of morbidity and mortality. The use of hs-TnT to diagnose post-CABG MI with a cut point of 10 times 99th percentile upper reference limit especially if associated with ECG and/or echocardiographic criteria predicts 30-day mortality.

Stercoral Perforation of the Rectum:

Stercoral perforation of the rectum is a rare disease. It is a potentially fatal complication of untreated chronic constipation. Presenting symptoms and signs are variable according to the site of the perforation. A 60-year-old male patient presented to the emergency room with dizziness and decreased level of consciousness. He was admitted for management under care of medical team as a case of urosepsis. Two days after admission he developed picture of Fournier gangrene. The underlying cause was found to be rectal perforation. Stercoral perforation is an emergency that can be missed if not highly suspected. We present a case of stercoral rectal perforation with picture of urosepsis and Fournier gangrene as presenting symptoms. Stercoral perforation is a potentially fatal disease with unspecific presentations that need to be highly suspected in patients with chronic constipation and severe sepsis.

P38α/JNK Signaling Restrains Erythropoiesis By Suppressing Ezh2-Mediated Epigenetic Silencing of Bim

A remarkable feature of erythropoiesis is the coordination of proliferation, differentiation and apoptosis of erythroid cells to precisely achieve erythropoietic homeostasis to avoid anemia and polycythemia. Anemia is a common disease arising from various causes, including Myelodysplastic syndromes, thalassemia, cancer chemotherapy, chronic kidney disease and hemorrhage. The pro-erythropoietic factor erythropoietin (EPO) is often employed for anemia therapy. However, questions have been raised about the safety of EPO given its potential for tumor promotion in cancer-related anemia. Moreover, many acute and chronic anemias, including hemolysis, sepsis and genetic bone marrow failure diseases such as Diamond-Blackfan anemia are untreatable with EPO. To overcome these hurdles, new molecular mechanisms need to be identified that physiologically restrain erythropoiesis by acting as molecular brakes to prevent over-active erythropoiesis caused by pro-erythropoietic signals. Inhibiting these restraining mechanisms could provide alternative approaches to treat anemia in an EPO-independent fashion. P38 MAPK (Mitogen-activated protein kinase) is an important pathway involved in diverse biological processes. P38 modulates cell proliferation, controls cell survival and decides cell fate during differentiation. P38 pathway functions mainly by phosphorylating and activating important transcription factors in response to different stimuli, including ATF2, CREB, and MEF2. There are four members within the P38 MAPK family, including P38α, P38β, P38γ, and P38δ. These members are encoded by different genes and have different tissue expression patterns. Among them, P38α is ubiquitously expressed. P38α modulates the function of different cell types. There are two distinct developmental defects reported in global P38α knockout mice by two separate groups using different mouse strains. One displayed embryonic death with highly anemic appearance due to reduced EPO production and another showed even earlier embryonic lethality due to placental developmental defects. In a P38α conditional mice model in which Cre recombinase was expressed in the whole mouse embryo but not in the placenta by crossing to MORE-Cre mice, no anemia or EPO defects were observed. However, the intrinsic and cell autonomous role of P38α in adult steady-state or stressful erythropoiesis has not been established. Loss of P38α causes activation of JNK in the liver. P38 inhibitors are in clinical trials and have the potential for the treatment of human disease. Therefore, it is important to understand the down-stream targets and functional outcomes induced by P38α deficiency. Using primary human erythroblasts derived from human CD34+ hematopoietic stem and progenitor cells (HSPCs) and P38α conditional knockout mice, we find that P38α acts as a molecular brake during anemia recovery through integrating apoptotic signals and by shortening the lifespan of erythroblasts to prevent potential over-active erythropoiesis caused by pro-erythropoietic signaling. Loss of P38α in erythroblasts activates JNK through augmented Map3k4 via a negative feedback circuit revealed by gene expression profiling. Functionally, JNK serves as a pro-survival signal independent of EPO by compromising Bim expression via stabilizing the epigenetic silencer Ezh2 in erythroblasts. JNK-controlled Cdk1 activity modulates full interaction of Ezh2 to the E3 ligase Smurf2 through multiple threonine phosphorylation sites within Ezh2. Our findings identify a key signaling cascade involving P38α/JNK/Cdk1/smurf2/Ezh2/Bim in fine tuning stress erythropoiesis. We propose that inhibition of P38α may provide an alternative strategy for the treatment of anemia. DisclosuresNo relevant conflicts of interest to declare.

Emerging Potential of Immediate Early Response Gene X-1 in Cardiovascular and Metabolic Diseases.

Immediate early response gene X‐1 (IEX‐1) or immediate early response 3 is an immediate early response gene that is highly expressed in epithelial, endothelial, and immune cells, including macrophages.1, 2, 3, 4 Similar to other immediate early response genes, its induction can be rapidly induced in response to several stimuli, such as UV light, inflammatory cytokines, and mechanical strain.4, 5, 6, 7, 8 Under stress, many immediate early response genes, such as c‐Fos, c‐Jun, c‐Myc, Egr‐1, and other zinc‐finger proteins, usually serve as transcription factors, activators, or repressors to regulate the transcriptional activity of several genes that are critical for a cell to appropriately respond to stress.4, 9, 10, 11, 12 However, IEX‐1 lacks a DNA binding domain and its putative transcription activity remains elusive.4, 13 Investigations from our laboratory show that IEX‐1 controls mitochondrial superoxide production by regulating the electron transport chain and oxidative phosphorylation.13, 14, 15, 16 This action of IEX‐1 might explain the transcriptional activity associated with IEX‐1 because the reactive oxygen species (ROS) at low levels can act as a signaling molecule to alter gene transcription through reduction‐oxidation–sensitive transcription factors or a signaling pathway, such as nuclear factor‐κB (NF‐κB) and nuclear factor erythroid 2‐related factor.17, 18, 19 Consistent with a key role of mitochondria in vascular and metabolic functions, IEX‐1 deficiency impairs vascular function and increases energy expenditure in mice. A key role of IEX‐1 in regulation of mitochondrial respiration and ROS production may also help to explain how IEX‐1 produces both antiapoptotic and proapoptotic actions in different cell types. Macrophages, the central player in the pathogenesis of many chronic inflammatory conditions, express high levels of IEX‐1. In agreement with the putative role of IEX‐1 in macrophage function, we recently identified a crucial role of IEX‐1 in many chronic conditions, including hypertension, sepsis, insulin resistance, obesity, and arthritis,16, 20, 21, 22 revealing previously unknown functions of IEX‐1 in cardiovascular and metabolic diseases. In this article, we reviewed the findings in IEX‐1 knockout mice from our laboratory and others and primarily focused on the roles of IEX‐1 in cardiovascular and metabolic disorders. We also alluded to the important findings from other laboratories that are relevant for its role in cardiovascular and metabolic diseases. In addition, an attempt is made to underline the involvement of IEX‐1 in inflammation and its possible link with the lipid‐mediated metabolic diseases. However, because of the limitations and scope of this article, we refrained from discussing an important role of IEX‐1 in many types of cancers that has been widely reported before.

Effects of antenatal indomethacin on ductus arteriosus early closure and on adverse outcomes in preterm neonates

Introduction: Premature birth is a leading cause of neonatal morbidity and mortality. Since gestational age at birth is the most important predictive factor of adverse neonatal outcomes, strategies to postpone premature labor are of major importance. Studies on tocolytic drugs show that COX inhibitors such as indomethacin are superior to others in terms of efficiency in delaying birth, but results concerning neonatal outcomes associated with prenatal exposure to these drugs show controversial results. Indomethacin is also used in the postnatal age for pharmacologic treatmentof patent ductus arteriosus (PDA), but no data concerning the effects of antenatal exposure on postnatal ductal patency are available.Methods: In this study, we focused primarily on the association between antenatal indomethacin (AI) and postnatal patency of ductus arteriosus while our secondary aim was to highlight any possible influence of AI exposure on adverse neonatal outcomes. We performed a retrospective analysis of 241 medical records of newborns born before 33 weeks' gestation and exposed to antenatal tocolysis. Obstetrical data and neonatal outcomes of newborns exposed to AI were compared to those of neonates exposed to other tocolytic drugs. Early ductal closure (EDC) was defined when functional echocardiography performed within 24 hours of life showed a closed duct. Occurrence of intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), respiratory distress syndrome (RDS), chronic lung disease (CLD), necrotizing enterocolitis (NEC), sepsis, and PDA were compared between the groups and the diagnosis of at least one of III–IV grade IVH, PVL, CLD, sepsis, surgical NEC, or death was defined as a severe outcome.Results: The univariate analysis showed that infants in the AI group were at a higher risk of IVH, CLD, RDS, sepsis, and PDA. The incidence of severe outcomes also appeared to be higher in this group, while no effect of AI on PDA was observed. Since we noticed that infants exposed to AI had a lower gestational age and worse clinical conditions at birth when compared to the controls, we considered this as a confounding factor. To overcome this bias, we performed a multivariate analysis that evidenced no significant role of AI on the occurrence of severe outcomes. On the other hand, a possible association was confirmed for all degrees of IVH (OR: 3.16, 95% CI : [1.41; 7.05]) and sepsis (OR: 2.81, 95% CI: [1.24; 6,28]).Conclusions: The unexpected result shown by the multivariate analysis was the association between AI exposureand EDC (OR: 2.52, 95% CI: [1.02; 6.21]). This result, which has never been evidenced in previous studies, has great clinical importance. It is well known that PDA is more frequent at lower gestational ages, thus reducing the incidence of PDA could lead to an improvement of overall outcomes in extremely preterm newborns.

Pleiotropic effects of proprotein convertase subtilisin/kexin type 9 inhibitors?

Current data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may affect many metabolic pathways beyond lowering LDL cholesterol. The aim of the present manuscript is to present these so-called pleiotropic effects of PCSK9 inhibitors. PCSK9 may affect the activity of other receptors beyond LDL receptors (LDLR), such as cluster of differentiation 36 (CD36), very-low-density-lipoprotein (VLDL) receptors, apolipoprotein (Apo) E receptors, LDLR-related protein 1 (LRP-1) and ATP-Binding Cassette Transporter (ABCA1). Thus, a role of PCSK9 in the development of atherosclerosis, in vascular wall inflammation and in platelet function has been suggested. Additionally, PCSK9 inhibitors may affect lipid variables beyond LDL cholesterol, carbohydrate variables, as well as they may affect brain and kidney function. Additionally, a controversial role of PCSK9 in sepsis, hepatitis C infection and Alzheimer's disease has been suggested. These possible pleiotropic effects of PCSK9 inhibitors need further research, as they may affect cardiovascular risk and provide further insights in the development of atherosclerosis and other diseases such as Alzheimer's disease or chronic viral infection and sepsis.

Evaluation of Medicare’s Bundled Payments Initiative for Medical Conditions

BackgroundThe Center for Medicare and Medicaid Innovation (CMMI) launched the Bundled Payments for Care Improvement (BPCI) initiative in 2013. A subsequent study showed that the initiative was associated with reductions in Medicare payments for total joint replacement, but little is known about the effect of BPCI on medical conditions.MethodsWe used Medicare claims from 2013 through 2015 to identify admissions for the five most commonly selected medical conditions in BPCI: congestive heart failure (CHF), pneumonia, chronic obstructive pulmonary disease (COPD), sepsis, and acute myocardial infarction (AMI). We used difference-in-differences analyses to assess changes in standardized Medicare payments per episode of care (defined as the hospitalization plus 90 days after discharge) for these conditions at BPCI hospitals and matched control hospitals.ResultsA total of 125 hospitals participated in BPCI for CHF, 105 hospitals for pneumonia, 101 hospitals for COPD, 88 hospitals for sepsis, and 73 hospitals for AMI. At baseline, the average Medicare payment per episode of care across the five conditions at BPCI hospitals was $24,280, which decreased to $23,993 during the intervention period (difference, −$286; P=0.41). Control hospitals had an average payment for all episodes of $23,901, which decreased to $23,503 during the intervention period (difference, −$398; P=0.08; difference in differences, $112; P=0.79). Changes from baseline to the intervention period in clinical complexity, length of stay, emergency department use or readmission within 30 or 90 days after hospital discharge, or death within 30 or 90 days after admission did not differ significantly between the intervention and control hospitals.ConclusionsHospital participation in five common medical bundles under BPCI was not associated with significant changes in Medicare payments, clinical complexity, length of stay, emergency department use, hospital readmission, or mortality. (Funded by the Commonwealth Fund.)

Predictors of in-hospital mortality in patients undergoing elective surgery in a university hospital: a prospective cohort

IntroductionMorbidity and mortality associated with urgent or emergency surgeries are high compared to elective procedures. Perioperative risk scores identify the non-elective character as an independent factor of complications and death. The present study aims to characterize the population undergoing non-elective surgeries at the Hospital de Clínicas de Porto Alegre and identify the clinical and surgical factors associated with death within 30 days postoperatively. MethodologyA prospective cohort study of 187 patients undergoing elective surgeries between April and May 2014 at the Hospital de Clínicas, Porto Alegre. Patient-related data, pre-operative risk situations, and surgical information were evaluated. Death in 30 days was the primary outcome measured. ResultsThe mean age of the sample was 48.5 years, and 84.4% of the subjects had comorbidities. The primary endpoint was observed in 14.4% of the cases, with exploratory laparotomy being the procedure with the highest mortality (47.7%). After multivariate logistic regression, age (odds ratio [OR] 1.0360, p<0.05), anemia (OR 3.961, p<0.05), acute or chronic renal insufficiency (OR 6.075, p<0.05), sepsis (OR 7.027, p<0.05), and patient-related risk factors for mortality, in addition to the large surgery category (OR 7.502, p<0.05) were identified. ConclusionThe high mortality rate found may reflect the high complexity of the institution's patients. Knowing the profile of the patients assisted helps in the definition of management priorities, suggesting the need to create specific care lines for groups identified as high risk in order to reduce perioperative complications and deaths.

Development of Perianal Sepsis Index (PASI) for assessing quality of life in chronic perianal sepsis

Fistula in ano causes significant morbidity and affects patients’ quality of life (QOL). A validated five-point Crohn’s Disease Perianal Activity Index (CDAI) has been reported, but there is no validated QOL/disease activity measure for patients with cryptoglandular sepsis (CS). We recruited 20 CS patients with active perianal sepsis requiring surgical intervention, who completed questionnaires of quantitative scores including the CDAI, the Fecal Incontinence Quality of Life (FIQOL), St. Mark’s Incontinence Score, and the 36-Item Short Form Health Survey (SF-36). Qualitatively, patients listed the five most significant impacts of perianal sepsis on their QOL. Disease activity was rated by the treating surgeon. The study also recruited 20 age-matched controls with no perianal disease. After analyzing each CDAI element, and using the patient and surgeon feedback, a simplified Perianal Sepsis Index (PASI) score was created. Qualitatively, pain (100%), discharge/leakage (80%), sexual function (60%), and depression (45%) were the most commonly stated impacts by patients. There were significant differences between patients and controls in the CDAI (9.8 vs. 0) and St. Mark’s scores (7.7 vs. 0.5), as well as in three domains of the FIQOL and SF-36 (p > 0.0I). After analyzing each CDAI element, patients were inaccurate in coding the type of perianal disease and degree of induration compared with their treating surgeon’s assessment. Removing disease type and degree of induration created a simplified PASI score. There were significant differences between patients and controls regarding CDAI and PASI scores (p < 0.05) but not St. Mark’s, FIQOL or SF-36 scores. The PASI score offers a method of self-quantifying the impact of perianal sepsis on QOL.

Cumulative positive fluid balance is a risk factor for acute kidney injury and requirement for renal replacement therapy after liver transplantation.

AIMTo analyze whether fluid overload is an independent risk factor of adverse outcomes after liver transplantation (LT).METHODSOne hundred and twenty-one patients submitted to LT were retrospectively evaluated. Data regarding perioperative and postoperative variables previously associated with adverse outcomes after LT were reviewed. Cumulative fluid balance (FB) in the first 12 h and 4 d after surgery were compared with major adverse outcomes after LT.RESULTSMost of the patients were submitted to a liberal approach of fluid administration with a mean cumulative FB over 5 L and 10 L, respectively, in the first 12 h and 4 d after LT. Cumulative FB in 4 d was independently associated with occurrence of both AKI and requirement for renal replacement therapy (RRT) (OR = 2.3; 95%CI: 1.37-3.86, P = 0.02 and OR = 2.89; 95%CI: 1.52-5.49, P = 0.001 respectively). Other variables on multivariate analysis associated with AKI and RRT were, respectively, male sex and Acute Physiology and Chronic Health Disease Classification System (APACHE II) levels and sepsis or septic shock. Mortality was shown to be independently related to AST and APACHE II levels (OR = 2.35; 95%CI: 1.1-5.05, P = 0.02 and 2.63; 95%CI: 1.0-6.87, P = 0.04 respectively), probably reflecting the degree of graft dysfunction and severity of early postoperative course of LT. No effect of FB on mortality after LT was disclosed.CONCLUSIONCumulative positive FB over 4 d after LT is independently associated with the development of AKI and the requirement of RRT. Survival was not independently related to FB, but to surrogate markers of graft dysfunction and severity of postoperative course of LT.

Impact of emergency department surge and end of shift on patient workup and treatment prior to referral to internal medicine: a health records review

BackgroundThe goal of this study was to determine if ED surge and end-of-shift assessment of patients affect the extent of diagnostic tests, therapeutic interventions and accuracy of diagnosis prior to...

Epidemiology and prognoses in a medical intermediate care unit.

The purpose of medical intermediate care units is the observation and treatment of patients with incipient or manifest organ failure. We wished to obtain data on which conditions result in admission to these units and the prognosis for these patients. All patients admitted to the medical intermediate care unit at Akershus University Hospital in 2014 were registered prospectively with reason for admission, period of hospitalisation, degree of severity, comorbidity, last place of hospitalisation prior to medical intermediate care and treatment limitations (do-not-resuscitate order and/or do-not-intubate order). Mortality in the hospital and one year after hospitalisation were registered retrospectively. Multiple regression analysis was performed with hospital mortality as the outcome variable. Altogether 1369patient hospitalisations for 1118 unique patients were included. The most frequent reasons for admission were pneumonia, chronic obstructive pulmonary disease, sepsis, poisonings and hyponatraemia. The degree of severity of the condition for which patients were admitted corresponded to that reported by intensive care departments in Norwegian local hospitals. A total of 13% died during their stay in hospital and a further 14% in the course of one year. The highest mortality was for patients with severe infection, cardiac failure and restrictive/neuromuscular respiratory disorder. The degree of severity, age, infection, comorbidity and ward as admitting unit were predictors of mortality during the hospitalisation period. Risk-adjusted mortality ratio of 0.64 satisfied the quality objective for intensive care departments (<0.7). A total of 5.6% of hospitalisations in the medical intermediate care unit entailed transfer to the intensive care ward. The degree of severity of the condition for which patients were admitted was high, and the treatment outcomes judged upon expected mortality were good. Medical intermediate care units can relieve pressure on wards with seriously ill patients without taking up intensive care beds.

Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors.

Sepsis, a complex disorder characterized by immune, metabolic, and neurological dysregulation, is the number one killer in the intensive care unit. Mortality remains alarmingly high even in among sepsis survivors discharged from the hospital. There is no clear strategy for managing this lethal chronic sepsis illness, which is associated with severe functional disabilities and cognitive deterioration. Providing insight into the underlying pathophysiology is desperately needed to direct new therapeutic approaches. Previous studies have shown that brain cholinergic signaling importantly regulates cognition and inflammation. Here, we studied the relationship between peripheral immunometabolic alterations and brain cholinergic and inflammatory states in mouse survivors of cecal ligation and puncture (CLP)-induced sepsis. Within 6 days, CLP resulted in 50% mortality vs. 100% survival in sham-operated controls. As compared to sham controls, sepsis survivors had significantly lower body weight, higher serum TNF, interleukin (IL)-1β, IL-6, CXCL1, IL-10, and HMGB1 levels, a lower TNF response to LPS challenge, and lower serum insulin, leptin, and plasminogen activator inhibitor-1 levels on day 14. In the basal forebrain of mouse sepsis survivors, the number of cholinergic [choline acetyltransferase (ChAT)-positive] neurons was significantly reduced. In the hippocampus and the cortex of mouse sepsis survivors, the activity of acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, as well as the expression of its encoding gene were significantly increased. In addition, the expression of the gene encoding the M1 muscarinic acetylcholine receptor was decreased in the hippocampus. In parallel with these forebrain cholinergic alterations, microglial activation (in the cortex) and increased Il1b and Il6 gene expression (in the cortex), and Il1b gene expression (in the hippocampus) were observed in mouse sepsis survivors. Furthermore, microglial activation was linked to decreased cortical ChAT protein expression and increased AChE activity. These results reinforce the notion of persistent inflammation-immunosuppression and catabolic syndrome in sepsis survivors and characterize a previously unrecognized relationship between forebrain cholinergic dysfunction and neuroinflammation in sepsis survivors. This insight is of interest for new therapeutic approaches that focus on brain cholinergic signaling for patients with chronic sepsis illness, a problem with no specific treatment.

Deceased donor liver transplant: Experience from a public sector hospital in India.

Deceased donor liver transplant (DDLT) is an uncommon procedure in India. We present our experience of DDLT from a public sector teaching hospital. A retrospective analysis of all DDLT was performed from April 2012 till September 2016. Demographics, intraoperative, donor factors, morbidity, and outcome were analyzed. During the study period, 305 liver transplants were performed, of which 36 were DDLT (adult 32, pediatric 4; 35 grafts; 1 split). The median age was 42.5 (1-62) years; 78% were men. The median donor age was 28 (1-77) years; 72.2% were men. About 45% of organs were procured from outside of Delhi and 67% of all grafts used were marginal. Three of 38 liver grafts (7.8%) were rejected due to gross steatosis. Commonest indication was cryptogenic cirrhosis (19.4%). The median model for end-stage liver disease sodium and pediatric end-stage liver disease scores were 23.5 (9-40) and 14.5 (9-22), respectively. Median warm and cold ischemia times were 40 (23-56) and 396 (111-750) min, respectively. Major morbidity of grade III and above occurred in 63.8%. In hospital (90days), mortality was 16.7% and there were two late deaths because of chronic rejection and biliary sepsis. The overall survival was 77.8% at median follow up of 8.6 (1-54) months. DDLT can be performed with increasing frequency and safety in a public sector hospital. The perioperative and long-term outcomes are acceptable despite the fact that most organs were extended criteria grafts.

Combination therapy of exendin-4 and allogenic adipose-derived mesenchymal stem cell preserved renal function in a chronic kidney disease and sepsis syndrome setting in rats.

Combined therapy with exendin-4 (Ex4) and allogenic adipose-derived mesenchymal stem cells (ADMSC) was tested against either therapy alone for protecting kidney function against chronic kidney disease (CKD) complicated by sepsis syndrome (SS) [i.e., by intraperitoneal injection of cecal-derived bacteria (1.0 × 104) cells/milliliter/total 5.0 cc].Adult-male-Sprague Dawley rats (n=36) were equally divided into group 1 (sham-control), group 2 (CKD), group 3 (CKD-SS), group 4 (CKD-SS-Ex4), group 5 (CKD-SS-ADMSC) and group 6 (CKD-SS-Ex4-ADMSC). At day 42 after CKD induction SS was induced. Thirty-minutes after SS induction, ADMSCs (2.0 ×106 cells) were intravenously administered to groups 5 and 6. Ex4 (10 μg/kg) was intraperitoneally administered groups 4 and 6 at 30 min and days 1 to 5 after SS induction. Animals were euthanized at day 47 after CKD induction. Kidney-injury score, collagen-deposition area, and creatinine/BUN levels were lowest in group 1, highest in group 3 and significantly higher in group 2 than in groups 4 to 6 in a progressively increasing manner (all P<0.0001). Protein expressions of inflammatory (MMP-9/TNF-α/NF-κB/IL-1ß/ICAM-1), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and fibrotic/DNA-damaged (Smad3/TGF-ß/γ-H2AX) biomarkers showed an identical pattern, whereas anti-fibrotic (BMP-2/Smad1/5), anti-apoptotic/endothelial-integrity (Bcl-2/eNOS) and podocyte-integrity (ZO-1/p-cadherin) biomarkers exhibited an opposite pattern of kidney-injury score among the six groups (all P>0.0001). Cellular expressions of inflammatory (CD14/CD68) and glomerulus/tubular-injury (WT-1/KIM-1) biomarkers displayed an identical pattern, whereas glomerulus/podocyte-component (dystroglycan/nephrin/ZO-1/fibronectin/p-cadherin) biomarkers showed an opposite kidney-injury score among the six groups (all P<0.0001). In conclusion, Ex4-ADMSC therapy effectively preserved renal function in the CKD-SS setting.

PP-18 Ranitidine-induced thrombocytopenia in a neonate-a case report and review of literature

Background Thrombocytopenia is defined as a plate-let count 72 hours)-onset thrombocy-topenia are caused by different categories of underlying conditions. Chronic fetal hypoxia and sepsis or necrotiz-ing enterocolitis are by far the most frequent causes of, respectively, early-and late-onset neonatal thrombocy-topenia.1,3 Methods We describe the clinical case of a SGA (small for gestational age) neonate who experienced a severe ranitidine-induced thrombocytopenia. An extensive lit-erature search was performed to document other cases of ranitidine-and H2-antagonist-induced thrombocyto-penia. Furthermore, other case reports of drug-induced thrombocytopenia in newborns were explored. Results We report on a late preterm male infant, who showed an unexpected, severe thrombocytopenia (8 × 109/L) at day 5 of life. He was born SGA and had also showed a mild early-onset thrombocytopenia with a low-est platelet count of 87 × 109/L on day 1, spontaneously normalising by day 3 (169 × 109/L). The low platelet count on day 5 only minimally responded to platelet transfu-sion. It did however recover completely within 5 days after cessation of ranitidine (4 × 0.5 mg/kg/day), which was started on day 3 of life in a context of feeding diffi-culties. Other causes of neonatal thrombocytopenia were explored and ruled out. The likelihood of an adverse drug reaction in this case was indicated as ‘probable’ on the Naranjo scale.4 Besides a brief report on a cimetidine-in-duced thrombocytopenia over 25 years ago,5 no other neonatal or paediatric cases of H2-antagonist-induced thrombocytopenia have been reported to date. Several adult cases have been published nevertheless.6 It seems that neonatalthrombocytopenia, although one of the most frequent haematological conditions in newborns, is only rarely attributed to an adverse drug reaction. Conclusion Neonatal thrombocytopenia is a frequent haematological abnormality and has a variety of causes. In rare cases, this low platelet count might be caused by an adverse drug reaction, supposedly immune-mediated. Although H2-antagonist are widely used in paediatric and neonatology departments, we describe the first case of a severe ranitidine-induced thrombocytopenia in a neo-nate. We believe that SGA infants are more at risk because of their inherent state of bone marrow depression at birth. Clinicians should be aware of the risks for (unexpected) adverse reactions, especially in routinely used drugs and in critically ill patients. Case reports may aid in expanding our knowledge of rare pharmacological complications.

Clinical characteristics of adrenal crisis in adult population with and without predisposing chronic adrenal insufficiency: a retrospective cohort study

BackgroundAdrenal crisis (AC) occurs in various clinical conditions but previous epidemiological studies in AC are limited to chronic adrenal insufficiency (AI) and sepsis. The aim of this study was to investigate characteristics of AC patients, including predisposing diseases and to describe candidate risk factors for AC such as comorbidities and glucocorticoid (GC) therapy.MethodsWe conducted a retrospective cohort study using a claims database on 7.4 million patients from 145 acute care hospitals between January 1, 2003 and April 30, 2014. We identified AC patients who met the following criteria: 1) disease name with ICD-10 corresponded with AI; 2) therapeutic GC administration (hydrocortisone equivalent dose ≥100 mg/day); 3) admission; and 4) age ≥18 years.ResultsWe identified 504 patients with AC (median age, 71 years; interquartile range, 59 to 80; 50.6% male). As predisposing conditions, primary AI and central AI accounted for 23 (4.6%) and 136 patients (27.0%), respectively. In the remaining AC patients (68.5%), comorbidities such as cancer, autoimmune diseases, and renal failure were frequent. The most frequent indication for hospitalization was AC (16.3%), followed by pituitary disease (14.7%), cancer (14.7%), AI-related clinical symptoms (11.5%), and infection (11.1%). Admission under oral GC treatment was reported in 104 patients (20.6%). Twenty-six patients were admitted within 14 days after GC cessation (5.2%).ConclusionsThese findings present an overview of patients with AC in general practice settings, clarifying that predisposing factors for AC were complicated and that patients other than those with chronic AI were older and had more comorbid conditions than those with primary and central AI.

Abstract P551: Platelet Activation is Associated with Pulmonary Edema and Renal Injury in a Rat Model of Polymicrobial Sepsis

Sepsis, life-threatening organ dysfunction due to a dysregulated host response to infection, is positively correlated with platelet activation. Furthermore, clinical studies have also shown that platelet activation is associated with sepsis severity, suggesting a role for platelets in sepsis pathophysiology. Despite this correlation, the underlying mechanisms by which activated platelets contribute to sepsis are under investigated. In preliminary studies, we set out to determine if platelet activation is associated with multi-organ dysfunction and injury in a rat model of chronic polymicrobial abdominal sepsis. Sepsis was induced via cecal ligation and puncture (CLP) followed by cecum removal 24 hours post-CLP. At 72 hours post-CLP, blood, urine, and tissues were collected for analysis. Platelet activation was measured via flow cytometry. Lung wet/dry ratio and plasma creatinine were measured to assess lung edema and renal injury, respectively. Platelet activation doubled in CLP rats versus Sham rats. Activated platelets increased from 3.8±1.7% of the gated population in Sham animals (n=5) to 9.2±1.9% of the gated population in CLP animals (n=5; p=0.07). Lung wet/dry ratio significantly increased from 3.9±0.2 in Sham (n=8) to 6.7±1 in CLP rats (n=8; p&lt;0.05). Furthermore, plasma creatinine increased by 33% from 0.55±0.3 mg/dL in Sham animals (n=6) to 0.73±0.06 mg/dL in CLP rats (n=8; p&lt;0.05), indicating a decrease in renal function. These data demonstrate, for the first time, an increase in platelet activation in response to CLP, and identifies an association of activated platelets with pulmonary edema and reduced renal function in the cecal ligation and puncture rat model of abdominal polymicrobial sepsis. Future studies will investigate the underlying mechanisms by which activated platelets contribute to multi-organ dysfunction and injury in sepsis.

Mutilation génitale féminine fatale chez une fille de 10 ans

Female genital mutilation (FGM) comprises all procedures involving partial or total removal of the external genitalia and/or any other procedures affecting the female genitalia, for cultural or religious reasons or for nontherapeutic purposes in general. FGM is responsible for a number of short-, medium-, and long-term complications that can engage the vital and functional prognosis, especially in African countries. We report on a case in a 10-year-old girl who underwent genital mutilation, a traditional type of total excision during the neonatal period. She was followed for urethral meatus stenosis, which then was complicated by obstructive chronic kidney failure and urinary sepsis, whose progression was fatal.